We have developed techniques for direct quantitative study of the cellular kinetics of the intestinal immune response in rats. Immunoblasts migrating to the gut lamina propria can be collected and examined in thoracic duct lymph while lamina propria plasma cells can be directly observed in gut sections. Specific antibody contained in these cells is identified by the fluorescent antibody technique and the class of immunoglobulin simultaneously determined by autoradiography with 125I-labeled purified F(ab')2 anti-rat immunoglobulin. We have already demonstrated primary and secondary types of responses of antibody-containing cells in gut lamina propria following immunization with cholera toxoid. We have also shown that intraintestinal antigen is essential in eliciting this response and determines the subsequent distribution of antibody-containing cells in the lamina propria. We propose to further examine the cellular kinetics of the intestinal immune response with the objective of providing a more rational basis for a practical approach to immunization against enteric infections such as those caused by V. cholerae and toxigenic E. coli. Specific objectives include: 1) definition of the duration of immunologic memory in the gut and of the role of oral and parenteral antigen and adjuvant in establishment of such memory, 2) study of the time of onset of the secondary immune response in the gut, comparing the cellular response with a direct measure of effective local immunity, 3) comparison of the cellular response to protein and LPS antigens and determination of the requirement for T cells in the intestinal immune response to these antigens, 4) study of the role of local exposure to antigen on the migration of thoracic duct IgA immunoblasts to other secretory sites (respiratory tract, breast) and on the migration of IgG and IgM immunoblasts to the gut mucosa, 5) study of antigen-trapping in the gut mucosa, especially after priming of the gut immunologic system, and 6) studies of the interrelationship between the gut immune response to the antigenically related enterotoxins of V. cholerae and E. coli. BIBLIOGRAPHIC REFERENCES: Pierce, N. F. Intestinal immunization with soluble bacterial antigens: The example of cholera toxoid. In: Acute diarrhoea in childhood, Ciba Foundation Symposium 42 (New Series) Elsevier/Exerpta Medica/North Holland, P.